3HRO

Crystal structure of a C-terminal coiled coil domain of Transient receptor potential (TRP) channel subfamily P member 2 (TRPP2, polycystic kidney disease 2)

3HRO の概要

• エントリーDOI: 10.2210/pdb3hro/pdb
• 関連するPDBエントリー: 3HRN
• 分子名称: Transient receptor potential (TRP) channel subfamily P member 2 (TRPP2), also called Polycystin-2 or polycystic kidney disease 2(PKD2) (2 entities in total)
• 機能のキーワード: coiled coil, helix bundle, trimer, calcium, disease mutation, glycoprotein, ion transport, ionic channel, membrane, phosphoprotein, polymorphism, transmembrane, transport, transport protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell projection, cilium membrane ; Multi-pass membrane protein : Q13563
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 5052.89

構造登録者

Yu, Y.,Ulbrich, M.H.,Li, M.-H.,Buraei, Z.,Chen, X.-Z.,Ong, A.C.M.,Tong, L.,Isacoff, E.Y.,Yang, J. (登録日: 2009-06-09, 公開日: 2009-07-28, 最終更新日: 2023-09-06)

主引用文献

Yu, Y.,Ulbrich, M.H.,Li, M.H.,Buraei, Z.,Chen, X.Z.,Ong, A.C.,Tong, L.,Isacoff, E.Y.,Yang, J.
Structural and molecular basis of the assembly of the TRPP2/PKD1 complex.
Proc.Natl.Acad.Sci.USA, 106:11558-11563, 2009

PubMed Abstract: Mutations in PKD1 and TRPP2 account for nearly all cases of autosomal dominant polycystic kidney disease (ADPKD). These 2 proteins form a receptor/ion channel complex on the cell surface. Using a combination of biochemistry, crystallography, and a single-molecule method to determine the subunit composition of proteins in the plasma membrane of live cells, we find that this complex contains 3 TRPP2 and 1 PKD1. A newly identified coiled-coil domain in the C terminus of TRPP2 is critical for the formation of this complex. This coiled-coil domain forms a homotrimer, in both solution and crystal structure, and binds to a single coiled-coil domain in the C terminus of PKD1. Mutations that disrupt the TRPP2 coiled-coil domain trimer abolish the assembly of both the full-length TRPP2 trimer and the TRPP2/PKD1 complex and diminish the surface expression of both proteins. These results have significant implications for the assembly, regulation, and function of the TRPP2/PKD1 complex and the pathogenic mechanism of some ADPKD-producing mutations.

PubMed: 19556541
DOI: 10.1073/pnas.0903684106

実験手法

X-RAY DIFFRACTION (1.9 Å)